1JPL

GGA3 VHS domain complexed with C-terminal peptide from cation-independent mannose 6-phosphate receptor

Summary for 1JPL

• Entry DOI: 10.2210/pdb1jpl/pdb
• Related: 1DVP 1ELK 1juq
• Descriptor: ADP-RIBOSYLATION FACTOR BINDING PROTEIN GGA3, Cation-Independent Mannose 6-phosphate receptor (3 entities in total)
• Functional Keywords: protein-peptide complex; vhs domain; dxxll sorting signal, signaling protein
• Biological source: Homo sapiens (human); More
• Cellular location: Golgi apparatus, trans-Golgi network membrane; Peripheral membrane protein: Q9NZ52; Lysosome membrane; Single-pass type I membrane protein: P11717
• Total number of polymer chains: 8
• Total formula weight: 84697.69

Authors

Misra, S.,Puertollano, R.,Bonifacino, J.S.,Hurley, J.H. (deposition date: 2001-08-02, release date: 2002-02-27, Last modification date: 2024-11-13)

Primary citation

Misra, S.,Puertollano, R.,Kato, Y.,Bonifacino, J.S.,Hurley, J.H.
Structural basis for acidic-cluster-dileucine sorting-signal recognition by VHS domains.
Nature, 415:933-937, 2002

PubMed Abstract: Specific sorting signals direct transmembrane proteins to the compartments of the endosomal-lysosomal system. Acidic-cluster-dileucine signals present within the cytoplasmic tails of sorting receptors, such as the cation-independent and cation-dependent mannose-6-phosphate receptors, are recognized by the GGA (Golgi-localized, gamma-ear-containing, ADP-ribosylation-factor-binding) proteins. The VHS (Vps27p, Hrs and STAM) domains of the GGA proteins are responsible for the highly specific recognition of these acidic-cluster-dileucine signals. Here we report the structures of the VHS domain of human GGA3 complexed with signals from both mannose-6-phosphate receptors. The signals bind in an extended conformation to helices 6 and 8 of the VHS domain. The structures highlight an Asp residue separated by two residues from a dileucine sequence as critical recognition elements. The side chains of the Asp-X-X-Leu-Leu sequence interact with subsites consisting of one electropositive and two shallow hydrophobic pockets, respectively. The rigid spatial alignment of the three binding subsites leads to high specificity.

PubMed: 11859375
DOI: 10.1038/415933a

Experimental method

X-RAY DIFFRACTION (2.4 Å)